Assessment of Ovarian Tumor Growth in Wild-Type and Lumican-Deficient Mice: Insights Using Infrared Spectral Imaging, Histopathology, and Immunohistochemistry

SIMPLE SUMMARY: Lumican, a small leucine-rich proteoglycan (SLRP), maintains extracellular matrix (ECM) integrity while inhibiting melanoma primary tumor development, as well as metastatic spread. The aim of this study was to analyze the effect of lumican on tumor growth of murine ovarian carcinoma. C57BL/6 wild type mice (n = 12) and lumican-deficient mice (n = 10) were subcutaneously injected with murine ovarian epithelial carcinoma ID8 cells, and sacrificed after 18 days. Label-free infrared spectral imaging (IRSI) generated high contrast IR images allowing identification of different ECM regions of the skin and the ovarian tumor. IRSI showed a good correlation with collagen distribution as well as organization, as analyzed using second harmonic generation imaging within the tumor area. The results demonstrated that lumican inhibited the growth of ovarian cancer mainly by altering collagen fibrilogenesis. ABSTRACT: Ovarian cancer remains one of the most fatal cancers due to a lack of robust screening methods of detection at early stages. Extracellular matrix (ECM) mediates interactions between cancer cells and their microenvironment via specific molecules. Lumican, a small leucine-rich proteoglycan (SLRP), maintains ECM integrity and inhibits both melanoma primary tumor development, as well as metastatic spread. The aim of this study was to analyze the effect of lumican on tumor growth of murine ovarian epithelial cancer. C57BL/6 wild type mice (n = 12) and lumican-deficient mice (n = 10) were subcutaneously injected with murine ovarian epithelial carcinoma ID8 cells, and then sacrificed after 18 days. Analysis of tumor volumes demonstrated an inhibitory effect of endogenous lumican on ovarian tumor growth. The ovarian primary tumors were subjected to histological and immunohistochemical staining using anti-lumican, anti-αv integrin, anti-CD31 and anti-cyclin D1 antibodies, and then further examined by label-free infrared spectral imaging (IRSI), second harmonic generation (SHG) and Picrosirius red staining. The IR tissue images allowed for the identification of different ECM tissue regions of the skin and the ovarian tumor. Moreover, IRSI showed a good correlation with αv integrin immunostaining and collagen organization within the tumor. Our results demonstrate that lumican inhibits ovarian cancer growth mainly by altering collagen fibrilogenesis.